Reproductive and Developmental Toxicity Study of Dibromoacetonitrile Administered to Sprague Dawley Rats in the Drinking Water

Abstract

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.

The potential toxicity of dibromoacetonitrile was evaluated using a short-term reproductive and developmental toxicity screen. This study design was selected to identify the process (development; female reproduction; male reproduction; various somatic organs/processes) that is the most sensitive to dibromoacetonitrile exposure.

The dose-range finding study initially used concentrations of 250-2000 ppm. This study was suspended after 4 days due to sharp reductions in fluid intake. The second dose-range finding study was conducted at concentrations of 0, 7, 20, 70, and 200 ppm of DBAN in the drinking water for two weeks. Based on a slight dose-related decrease in mean body weight and a decrease in water consumption, concentrations of 0, 15, 50, and 150 ppm were selected for the main study, which utilized one group of male rats (10 per dose level) and two groups of female rats designated as Group A (peri-conception exposure, 10 per dose level) and Group B (gestational exposure, 13 per dose level). Control animals received deionized water, the vehicle.

During the treatment period, all animals survived to the scheduled necropsy and there were no clinical signs of general toxicity noted at any dose level. Over the course of the study, water consumption was decreased in the 50 ppm males and B females by 15-32% while water consumption was decreased by 28-49% at most of the intervals in all 150 ppm groups. The overall average calculated consumption of DBAN for Groups 2-4 was 1.7, 4.5, and 9.9 mg/kg/day, respectively. Male and female mean absolute body weights, clinical observations, and gross findings were comparable across dose groups, as were male organ weights, organ-to-body weight ratios, and clinical chemistry and hematology endpoints. Male feed consumption in the 150 ppm group was reduced by 11-18% at the first two measurement intervals only. There were no treatment-related reproductive effects in the males or females.

Results of this study indicate that DBAN treatment reduced water consumption in the 50 and 150 ppm dose levels in males and females in the absence of reproductive toxicity. A maximum tolerated dose in both males and females was achieved at 50 ppm DBAN based on a greater than 20% reduction in water consumption. From these data, DBAN may be a taste-aversive at 50 or 150 ppm in male and female rats, but is not a reproductive toxicant in males or females at dose levels up to 150 ppm DBAN.